Author(s)

Kevin M. Rice¹, Ravi Kumar Arvapalli¹, Eric R. Blough^1,2

¹Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
²Department of Pharmacy Science and Research, School of Pharmacy, Marshall University, Huntington, WV, USA.

Background: Vein graft failure after bypass surgery is greatly increase in patients with diabetes mellitus. The cellular mechanisms underlying the cause of this failure are largely unexplored. Protein kinase B/AKT is a mechanically sensitive regulator of cellular growth and apoptosis. Herein we examine whether diabetes affects the regulation of AKT in response to increased venous loading. Methods: Inferior venae cavae (IVC) from the non-diabetic lean (LNZ) and the diabetic obese syndrome X Zucker(OSXZ) rats were isolated and incubated ex vivo under basal or pressurized conditions (120 mmHg). Protein expression, basal activation and the ability of increased pressure to activate AKT3 and apoptosis-related signaling were evaluated by immunoblot analysis. Results: Compared to that seen in the non-diabetic lean animals, increased venous pressure in the OSXZ rats was not characterized by increases in APAF-1 concentration, XIAP proteolysis, AIF cleavage, or Bad phosphorylation. This evidence of decreased apoptotic signaling was associated with increased basal p-AKT3 levels (+136% ± 13% P < 0.05 higher in the OSXZ vs. LNZ IVC). Conclusion: These data suggest that diabetes-associated increases in p-AKT3 may alter the ability of the IVC to undergo pressure induced apoptosis-related signaling. Further investigation is required to determine whether these changes are associated with the increased vein graft attrition seen in the diabetic population.

Diabetes, Zucker Rat, Inferior Venae Cavae, AKT3

Rice, K. , Arvapalli, R. and Blough, E. (2015) Hyperglycemia Induced Changes in Vascular AKT3 May Inhibit Pressure-Induced Apoptosis in the Rat Inferior Venae Cavae. Open Journal of Endocrine and Metabolic Diseases, 5, 41-50. doi: 10.4236/ojemd.2015.54006.